Rouigari Maedeh, Dehbashi Moein, Ghaedi Kamran, Pourhossein Meraj
Isfahan Neuroscience Research Center (INRC), Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
Genetics Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.
Cell J. 2018 Jul;20(2):150-156. doi: 10.22074/cellj.2018.4901. Epub 2018 Mar 18.
For the first time, we used molecular signaling pathway enrichment analysis to determine possible involvement of miR-126 and IRS-1 in neurotrophin pathway.
In this prospective study, Validated and predicted targets (targetome) of miR-126 were collected following searching miRtarbase (http://mirtarbase.mbc.nctu.edu.tw/) and miRWalk 2.0 databases, respectively. Then, approximate expression of miR-126 targeting in Glioma tissue was examined using UniGene database (http://www.ncbi. nlm.nih.gov/unigene). In silico molecular pathway enrichment analysis was carried out by DAVID 6.7 database (http://david. abcc.ncifcrf.gov/) to explore which signaling pathway is related to miR-126 targeting and how miR-126 attributes to glioma development.
MiR-126 exerts a variety of functions in cancer pathogenesis via suppression of expression of target gene including PI3K, KRAS, EGFL7, IRS-1 and VEGF. Our bioinformatic studies implementing DAVID database, showed the involvement of miR-126 target genes in several signaling pathways including cancer pathogenesis, neurotrophin functions, Glioma formation, insulin function, focal adhesion production, chemokine synthesis and secretion and regulation of the actin cytoskeleton.
Taken together, we concluded that miR-126 enhances the formation of glioma cancer stem cell probably via down regulation of IRS-1 in neurotrophin signaling pathway.
我们首次使用分子信号通路富集分析来确定miR-126和胰岛素受体底物1（IRS-1）在神经营养因子通路中可能的参与情况。
在这项前瞻性研究中，分别通过搜索miRtarbase（http://mirtarbase.mbc.nctu.edu.tw/）和miRWalk 2.0数据库收集miR-126的验证和预测靶点（靶标组）。然后，使用UniGene数据库（http://www.ncbi.nlm.nih.gov/unigene）检测miR-126在胶质瘤组织中的靶向近似表达。通过DAVID 6.7数据库（http://david.abcc.ncifcrf.gov/）进行计算机分子通路富集分析，以探索哪些信号通路与miR-126靶向相关以及miR-126如何影响胶质瘤的发展。
miR-126通过抑制包括磷脂酰肌醇-3-激酶（PI3K）、KRAS、表皮生长因子样蛋白7（EGFL7）、IRS-1和血管内皮生长因子（VEGF）等靶基因的表达，在癌症发病机制中发挥多种功能。我们利用DAVID数据库进行的生物信息学研究表明，miR-126靶基因参与了多种信号通路，包括癌症发病机制、神经营养因子功能、胶质瘤形成、胰岛素功能、粘着斑产生、趋化因子合成与分泌以及肌动蛋白细胞骨架的调节。
综上所述，我们得出结论，miR-126可能通过下调神经营养因子信号通路中的IRS-1来促进胶质瘤癌干细胞的形成。
